{"id":10,"date":"2021-02-24T13:29:07","date_gmt":"2021-02-24T13:29:07","guid":{"rendered":"https:\/\/geiselmed.dartmouth.edu\/supattapone\/?page_id=10"},"modified":"2021-02-24T15:22:22","modified_gmt":"2021-02-24T15:22:22","slug":"molecular-mechanism-of-prion-infectivity","status":"publish","type":"page","link":"https:\/\/geiselmed.dartmouth.edu\/supattapone\/research\/molecular-mechanism-of-prion-infectivity\/","title":{"rendered":"Molecular Mechanism of Prion Infectivity"},"content":{"rendered":"

Background<\/h2>\n

Prions<\/a> are infectious agents of fatal brain diseases that include: Creutzfeldt Jakob Disease (CJD) and kuru<\/a> in humans, bovine spongiform encephalopathy<\/a> (BSE) in cows, Chronic Wasting Disease<\/a> (CWD) in deer and elk, and scrapie<\/a> in sheep and goats. Interestingly, prions are unorthodox infectious agents<\/a> because they do not contain nucleic acids. Instead, a membrane-bound glycoprotein called the prion protein (PrP) appears to be the molecule responsible for the transmission of prion disease. The native, cellular conformer of PrP, designated PrPC<\/sup>, is expressed in all normal mammals. When an animal contracts prion disease, the PrPC<\/sup> molecules in the brain of that animal undergo a conformational change to a pathogenic conformer designated PrPSc<\/sup>. This pathogenic conformer is infectious, promoting conformational change to create more PrPSc<\/sup> molecules, and its formation leads to the death of neurons.<\/p>\n

Interestingly, recent studies have shown that a number of other neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis (ALS) apparently also spread through the brain using prion-like mechanisms. Furthermore, prion-like proteins have also been found in non-mammalian organisms such as bacteria and yeast, where they can serve normal biological functions. Thus, studies of infectious prions are likely to have far-reaching impact in both medicine and biology.<\/p>\n

Currently, the structure and composition of infectious prions, as well as the mechanisms by which these agents replicate and destroy neurons are unknown<\/a>. These questions represent key areas of investigation for our laboratory. Significant scientific advances made in our laboratory include the de novo formation of infectious prions from defined, non-infectious components in vitro<\/a>, the identification of RNA<\/a> and phosphatidylethanolamine<\/a> (PE) as endogenous cofactors in prion formation, and the demonstration that such cofactors encode infectivity and strain properties<\/a>.<\/p>\n

Images<\/h2>\n